title: Relation between toxicity and carcinogenesis in the kidney: an heuristic hypothesis.
abstract: Cellular toxicity and cellular carcinogenesis are closely linked. In the kidney, this relationship has been emphasized by the recent discovery of a number of putatively non-mutagenic chemicals that result in acute and chronic toxicity and ultimately in carcinogenesis, especially in the male rat. Many, but not all such compounds, result in renal PTE phagolysosomal overload. At the same time, known metabolites of other carcinogens, e.g., HCBD and FBPA, result in acute renal injury and/or necrosis, followed by chronic tubular disease, interstitial nephritis, and ultimately carcinogenesis. A series of cell mechanisms have been suggested that lead from acute cell injury to altered control of cell division. These mechanisms appear to involve ion deregulation, (especially [Ca2+]i) resulting from a variety of continued injuries, (e.g., oxidative stress from inflammatory cells) and ultimately leading to altered gene expression.
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore.
authors.forename: B F
authors.initials: BF
authors.lastname: Trump
authors.forename: T W
authors.initials: TW
authors.lastname: Jones
authors.forename: K A
authors.initials: KA
authors.lastname: Elliget
authors.forename: M W
authors.initials: MW
authors.lastname: Smith
authors.forename: P C
authors.initials: PC
authors.lastname: Phelps
authors.forename: A
authors.initials: A
authors.lastname: Maki
authors.forename: I K
authors.initials: IK
authors.lastname: Berezesky
mesh_terms: D000818:Animals; D002273:Carcinogens; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000139:chemically induced; D007680:Kidney Neoplasms / Q000139:chemically induced*; D010084:Oxidation-Reduction; D011817:Rabbits
chemical_list: D002273:Carcinogens